Enterobacter cloacae (E. cloacae) belongs to the bacterial family Enterobacteriaceae, whose diverse members are Gram-negative rods that are glucose fermenters and nitrate reducers. These organisms are found free-living in nature and as part of the indigenous flora of human and animals. They grow rapidly under aerobic and anaerobic conditions and are metabolically active, utilizing a variety of substrates. Most species are opportunistic pathogens (Kenneth Ryan, Enterobacteriaceae, Chap. 20, Medical Microbiology, An Introduction to Infectious Diseases, Second Edition, Editor, John C. Sherris, Elsevier, New York, 1990).
E. cloacae is an ornithine-positive, lysine-negative pathogen that can be associated with urinary tract and respiratory tract infections. The bacteria produces endotoxins which as aerosols can penetrate into the lungs causing fever, coughing, difficulty in breathing and wheezing (Fairley, T. and Gislason, S., 1986–1997, Environmed Research Inc). E. cloacae is becoming progressively common in newborns in Neonatal Intensive Care Units (NICU) (Shi, Z. Y., et al, 1996, J. Clin. Microbiol. 34:2784–2790; Cordero, L., et al, 1997, Pediatr. Infect. Dis. J. 16:18–23; Acolet, D., et al, 1994, J. Hosp. Infect. 28:273–286). A study at Children's Hospital in Michigan showed a four-fold increase in Enterobacter in patients with bacteremia between 1989 and 1992. E. cloacae accounted for 74% of the isolates. Twenty eight percent of the infected children went into shock and six percent died (Andresen, J., et al, 1994, Pediatr. Infect. Dis. J. 13: 787–792). An outbreak of multidrug-resistant E. cloacae lasted for 4 months in the NICU in China (Shi, Z. Y., et al, 1996, J. Clin. Microbiol. 34:2784–2790). Outbreaks have also occurred in surgical wards (Burchard, K. W., et al, 1986, Surgery 100:857–862) and burn units (Markowitz, S. M., et al, 1983, J. Infect. Dis. 148:18–23). E. cloacae has also been shown to be the causative agent in a case of gas gangrene (Fata, F., et al, 1996, South Med. J. 89:1095–1096).
Epidemiology of E. cloacae is not completely understood, although studies of infection and colonization point to the endogenous flora of the patients. Molecular typing results of 141 strains of E. cloacae from broad geographic areas in the United States (from the National Surveillance Program: SCOPE) indicated that although clonal spread of a single strain was observed within a given institution most of the episodes of bacteremia were caused by strains unique to the individual patients. Therefore, selection of mutant subpopulations within each endogenous infection can be caused by drug exposure (Pfaller, M. A., 1997, Diagn. Microbiol. Infect. Dis. 28:211–219).
Antibiotic resistance is a major problem in the control of infectious diseases. Strains of E. cloacae resistant to broad-spectrum penicillins and beta-lactamase-stable cephalosporins occurs at a frequency of 107 to 106 (Kadima, T. A. and Weiner, J. H., 1997, Antimicrobiol. Agents Chemother. 41:2177–2183; Lampe, M. F., et al, Antimicrob. Agents Chemother. 21:655–660; Lindberg, F., et al, Rev. Infect. Dis. 8 [Suppl 3]:S292–S304). Selected fluroquinolones have often been successfully administered to patients with urinary tract infections; however, E. cloacae has become resistant to many of them (Deguchi, T., et al, 1997, Antimicrobiol. Agents Chemother. 41: 2544–2546). Some resistance has been attributed to plasmid-containing E. cloacae and some to the E. cloacae chromosome. In Holland, two different resistant strains of E. cloacae have been identified. The Amsterdam strain (resistant to ceffotaxin and piperacillin) exhibits depressed chromosomal Class 1 beta-lactamase, whereas the Rotterdam strain (resistant to cefuroxine) favors the spread of a plasmid encoding TEM-2 beta-lactamase (Namavar, F., 1997, BIO 99–53 99–606615). Resistant strains of E. cloacae developed within 6 days in nearly 50% of the E. cloacae-infected intensive care patients with pulmonary complications treated with cefotaxime (Fussle, et al., 1994, Clin. Investig. 72:1015–1019). While several antimicrobial agents retain potent activity against the highly resistant organisms (Pfaller, M. A., 1997, Diagn. Microbiol. Infect. Dis. 28:211–219), constant exposure to these agents may eventually result in resistance.
E. cloacae has been shown to be beneficial to plants in the control of diseases caused by bacteria (Bacon, C. W., et al., PCT publication WO 97/24433). As a biocontrol agent, E. cloacae coated onto cucumber seed has protected the seed from a lethal infection of the fungus Pythium ultimum (Nelson, E. B., et al, 1992, Can. J. Plant Pathol. 14:106–114). Nutritional mutants of E. cloacae were also protective and it has been suggested that mutant strains would be beneficial for an environmental containment strategy (Roberts, D. P., et al, 1994, Plant Science [Limerick], 10183–89).